This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The genetic study of complex diseases like cancer has gained increased attention over the past several years and has become more and more important as we discover likely common metabolic pathways for several common traits. The primary genetic tool for such studies, to this point, has been linkage analysis. However, the ability of linkage analysis to localize a locus potentially segregating for susceptibility/protective genotypes is limited to, at best, a region of 5-10 centimorgans (cM). In parallel with the development of more sophisticated molecular tools to investigate the genome, increasing evidence has been collected on risk factors leading to the development and decreased survivorship of cancer. Obesity and metabolic dysfunction have been at the top of this list. In fact, the epidemic increase in obesity and metabolic dysfunction over the last 30 years (doubling in adults and tripling in children) portend a substantial increase in cancer morbidity and mortality. This study assesses the relationship between indices of metabolic pathways implicated in cancer, including insulin resistance (fasting and post glucose load insulin and glucose levels) and the candidate gene region for insulin-like growth factor 1 (IGF1).This study also assesses potential genetic variation as a source of variation in traits comorbid with cancer. We have completed biomarker assays for IGF levels in a large cohort of pedigrees (1400 individuals). We have genotyped SNPs in IGF1, IGFBP1 and IGFBP3 gene. Association analysis and modeling of these pathways is currently underway.